Homeostatic regulation of neuronal firing rate is a fundamental problem faced by spiking neurons. However different neurons must regulate their firing rates around different firing rate set points and the circuit effects of cellular homeostasis are different for excitatory, inhibitory and modulatory neurons. Cell type specific biophysical and molecular mechanisms of firing rate homeostasis will be explored in transgenic mice that permit targeting of specific neocortical and modulatory cell types. Understanding how core FRSP machinery is modified and integrated with different sets of effectors in order to achieve homeostatic regulation across different cell types in a circuit is a crucial aspect of understand how FRSPs are implemented, and of understanding how their malfunction may alter circuit operation in disease. RELEVANCE: The ability of brain circuits to maintain stable firing rates is disrupted in a variety of developmental brain disorders, degenerative diseases and after brain damage. Subsequent compensatory changes in cellular and sjoiaptic properties can lead to epilepsy or other forms of abnormal activity. Understanding the molecular pathways by which diverse neuronal cell types regulate their firing in response to changes in activity may allow prevention of maladaptive homeostatic changes brought into play by other circuit pathologies.